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Nuclear Factor Kappa-B: Bridging Inflammation and Cancer
Published in Surinder K. Batra, Moorthy P. Ponnusamy, Gene Regulation and Therapeutics for Cancer, 2021
Mohammad Aslam Khan, Girijesh Kumar Patel, Haseeb Zubair, Nikhil Tyagi, Shafquat Azim, Seema Singh, Aamir Ahmad, Ajay Pratap Singh
Several regulatory mechanisms and crosstalks have been proposed for the non-canonical pathway of NF-κB activation. During stimulation, IKKα exhibits negative feedback mechanism and destabilizes NIK levels while another kinase, TANK-binding kinase1 (TBK1), also phosphorylates and controls stability of NIK in a signal-dependent manner [74, 75]. De-ubiquitinase, OTU deubiquitinase 7B (OTUD7b), acts as negative regulator for the activation of non-canonical NF-κB pathway. After binding to TRAF3, OUTD7b deubiquitinates TRAF3 and indirectly controls the levels of NIK in a signal-dependent manner [76].
BAP1 Tumor Predisposition Syndrome
Published in Dongyou Liu, Handbook of Tumor Syndromes, 2020
Mutations in the BAP1 gene may produce prematurely terminated BAP1 protein, reduce cellular BAP1 levels, and alter the ubiquitin carboxyl-terminal hydrolase domain, thus affecting the deubiquitinase activity of BAP1. Reduced nuclear and cytoplasmic activities of BAP1 decrease IP3R3 levels and Ca2+ flux, and prevent cells containing damaged DNA from apoptosis. There is evidence that carriers of germline BAP1 mutations with only one normal BAP1 allele have 50% less of cellular BAP1 than normal persons. Furthermore, cells from carriers of germline BAP1 mutations display reduced ability to repair DNA by homologous recombination (due to the reduced nuclear BAP1 levels) and impaired apoptosis upon exposure to asbestos, ultraviolet light, and irradiation (due to the reduced mitochondrial Ca2+ levels), leading to increased vulnerability to malignant transformation [24].
Human Noroviruses
Published in Dongyou Liu, Handbook of Foodborne Diseases, 2018
G. Sanchez, W. Randazzo, D.H. D'Souza
Besides the traditional approaches, interferons (peptides with antiviral activity) as viable approaches to combat HNoV infection are being researched as summarized in Prasad et al.221 Type I interferons are reported to inhibit HNoV replication in a replicon system in vitro, without any reports on human studies, while both type I and type II interferons can inhibit MNV replication and type III interferon, interferon lambda, can clear chronic MNV infection.244,245 RNA interference model studies that prevent HNoV replication and design of deubiquitinase inhibitors that target host factors during the viral life cycle are other research avenues.221,222 It appears that the combined use of antivirals and vaccines may be needed to prevent the spread of emerging HNoVs or to alleviate their disease symptoms or both.221
Bone Marrow Stromal Cell-Secreted Extracellular Vesicles Containing miR-34c-5p Alleviate Lung Injury and Inflammation in Bronchopulmonary Dysplasia Through Promotion of PTEN Degradation by Targeting OTUD3
Published in Immunological Investigations, 2023
Xiao He, Juan Kuang, Yijing Wang, Guofeng Lan, Xuekai Shi
The Starbase database utilized in our study predicted that ovarian tumor deubiquitinase 3 (OTUD3) bound to miR-34c-5p. OTUD3, a deubiquitinase, can stabilize proteins by deubiquitinating K48-linked ubiquitination and modulate protein activity by deubiquitinating K11- or K63-linked ubiquitination (Shen et al. 2021). Reportedly, OTUD3 suppressed tumorigenesis by promoting the stability of phosphatase and tensin homolog (PTEN) through deubiquitination (Yuan et al. 2015). Moreover, PTEN downregulation participates in the repressive impacts of microvesicles from human umbilical cord MSCs on alveolarization and lung inflammation in BPD rats (Zhou et al. 2022). These backgrounds contribute to the hypothesis that BMSC-EVs containing miR-34c-5p (BMSC-EVs-miR-34c-5p) might affect BPD progression through the OTUD3/PTEN axis. Therefore, this study was designed to confirm this speculation, providing a novel therapeutic direction for BPD.
Therapeutic strategies for Parkinson’s disease: promising agents in early clinical development
Published in Expert Opinion on Investigational Drugs, 2020
Margherita Fabbri, Santiago Perez-Lloret, Olivier Rascol
Silencing of SNCA using small hairpin RNA and antisense oligonucleotides to reduce α-synuclein synthesis has provided conflicting results in preclinical studies [68–70], and no clinical trials have yet been conducted. Indeed, silencing approaches might disrupt the unknown physiological role of the protein. However, similar approaches are entering Phase Ib/II programs for huntingtin protein in patients with Huntington disease, and might soon be applicable in PD. At the preclinical stage, successful neuroprotection has been reported via enhancement of proteasomal activity by means of a small-molecule inhibitor of USP13 (a proteasome-associated deubiquitinase) or by an increase in autophagy in both in vitro and in vivo models of PD [71]. This might be promising for the future, although the safety of such compounds for long-term use needs to be investigated.
The role of plant expression platforms in biopharmaceutical development: possibilities for the future
Published in Expert Review of Vaccines, 2019
Other Zoonotic diseases such as Chikungunya and Middle Eastern Respiratory syndrome virus are also being addressed using plant-based approaches. Chikungunya is a mosquito-transmitted virus that causes fever, headaches and severe joint pain. Multiple efforts have been made to generate a plant-made vaccine to Chikungunya with some success [46,47]. Monoclonal antibodies to Chikungunya virus have been successfully constructed and used both as a diagnostic tool and as a therapeutic for the poor [48]. Similarly, MERS, which is endemic in the world’s camel population, transmitted by aerosol and, with a mortality rate in humans approaching 40%, has been designated as a potential emerging threat [49]. A plant-made version of a ubiquitin variant, which binds to the viral deubiquitinase enzyme and blocks infection, has been constructed in several virus expression systems and is currently being explored as an efficacious means to block transmission as well as disease symptoms (personal communication).